This one is hard to understand.
http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=57779
A key protein, which may be activated to protect nerve cells from
damage during heart failure or epileptic seizure, has been found to
regulate the transfer of information between nerve cells in the brain.
The discovery, made by neuroscientists at the University of Bristol and
published in Nature Neuroscience and PNAS, could lead to novel new
therapies for stroke and epilepsy.
A key protein, which may be
activated to protect nerve cells from damage during heart failure or
epileptic seizure, has been found to regulate the transfer of
information between nerve cells in the brain. The discovery, made by
neuroscientists at the University of Bristol and published in Nature
Neuroscience and PNAS, could lead to novel new therapies for stroke and
epilepsy.
The research team, led by Professor Jeremy Henley and Dr
Jack Mellor from Bristol’s Medical School, has identified a protein,
known as SUMO, responsible for controlling the chemical processes which
reduce or enhance protection mechanisms for nerve cells in the brain.
These
key proteins produce subtle responses to the brain’s activity levels to
regulate the amount of information transmitted by kainate receptors -
responsible for communication between nerve cells and whose activation
can lead to epileptic seizures and nerve cell death.
Protein
function is controlled by altering their structure in processes that can
be independent or inter-related including phosphorylation,
ubiquitination and SUMOylation. In the present work it is shown that
phosphorylation of kainate receptors on its own promotes their activity.
However, phosphorylation also facilitates SUMOylation of kainate
receptors that reduces their activity. Thus there is a dynamic and
delicate interplay between phosphorylation and SUMOylation that
regulates kainate receptor function.
This fine balance between
phosphorylation and SUMOylation is dependent on brain activity levels
where damaging activity that occurs during stroke or epilepsy will
enhance SUMOylation and therefore reduce kainate receptor function to
protect nerve cells.
Dr Mellor, Senior Lecturer from the
University’s School of Physiology and Pharmacology, said: “Kainate
receptors are a somewhat mysterious but clearly very important group of
proteins that are known to be involved in a number of diseases including
epilepsy. However, we currently know little about what makes kainate
receptors so important. Likewise, we also know that SUMO proteins play
an important role in neuroprotection. These findings provide a link
between SUMO and kainate receptors that increases our understanding of
the processes that nerve cells use to protect themselves from excessive
and abnormal activity.”
Professor Henley added: “This work is
important because it gives a new perspective and a deeper understanding
of how the flow of information between cells in the brain is regulated.
The team has found that by increasing the amount of SUMO attached to
kainate receptors – which would reduce communication between the cells –
could be a way to treat epilepsy by preventing over-excitation of the
brain’s nerve cells.”
The research follows on from previous findings
published in Nature that discovered SUMO proteins target the brain’s
kainate receptors altering their cellular location.
The research
teams comprised academics from the University of Bristol’s MRC Centre
for Synaptic Plasticity and the Division of Neuroscience in the School
of Physiology & Pharmacology and the School of Biochemistry. This
work was supported by the Wellcome Trust, Biotechnology and Biological
Sciences Research Council (BBSRC), European Research Council (ERC),
Medical Research Council (MRC) and EMBO
